Selective inhibition of E-selectin, ICAM-1, and VCAM in endothelial cells

✍ Scribed by Karl M. Stuhlmeier; Vilmos Csizmadia; Qi Cheng; Hans Winkler; Fritz H. Bach

• Book ID: 102824390
• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 544 KB
• Volume: 24
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830240938

✦ Synopsis

Endothelial cells, as they normally exist in the vasculature as quiescent cells, perform several functions. In an inflammatory response, endothelial cells are activated to up-regulate a number of genes, including E-selectin (ELAM-l), VCAM-1, ICAM-1, interleukin (IL)-l, IL-8 and plasminogen activator inhibitor-1 (PAI-l).Very little is known about factors that regulate the activation process. We describe here that a heat-stable protein, normally present in the a-globulin fraction of serum, inhibits induced expression of E-selectin, ICAM-1, and VCAM-1 in vitro and also impedes the accumulation of mRNA for these molecules. Inhibition of E-selectin, the only gene tested in this respect, is at the level of transcription. At the same time, the a-globulins do not, under the same conditions, repress mRNA accumulation for IL-1, IL-8, or PAI-1. The effect of the inhibitor does not relate to constraints on function of nuclear-factor xB, the induced activity of which is not interfered with at the early time points at which the suppression of these three genes is seen.